AIDS is a clinically defined medical illness which can result from an infection with HIV. The definition of AIDS has been published and continually revised by the Centers for Disease Control (Atlanta). It is generally accepted that progression of the infection gradually renders the individual immunodeficient, and as a result, HIV leads to death from fatal opportunistic infections such as Pneumocystis carinii pneumonia. The mechanism by which HIV infection results in AIDS is believed to be mediated through the binding of HIV to a subset of T cells which are identified by the CD4 and CD3 surface antigens. By infecting and subsequently destroying the CD4 subset of lymphocytes, the individual infected with HIV loses the ability to respond to certain infectious agents.
HIV infections progress through a number of clinical stages which may be distinguished in both clinical and laboratory findings. One presently accepted classification system for defining and staging the progress of HIV infection from initial exposure through the diagnosis of AIDS is described in the Walter Reed Classification System. This system is set out in Table I.
TABLE I ______________________________________ CD4 Delayed Oppor- Chronic Cells Hyper- tunistic Ab/ Lymphad- (cells/ sensi- Infec- Stage Virus enopathy mm.sup.2) tivity Thrush tions ______________________________________ WR0 - - &gt;400 Normal - - WR1 + - &gt;400 Normal - - WR2 + + &gt;400 Normal - - WR3 + + &lt;400 Normal - - WR4 + + &lt;400 Partial - - WR5 + + &lt;400 Complete + - and/or WR6 + + &lt;400 Complete + + ______________________________________
As may be seen from Table I, a number of separate criteria go into evaluating and defining each of the several stages. For example, the presence or absence of antibodies (Abs) to HIV or the presence or absence of detectable virus itself are used as an indication of initial exposure to HIV (WR1). These infected patients exhibit few, if any, signs of AIDS and may be considered asymptomatic but seropositive. Subsequently, the number of CD4 cells falls, the further the disease has progressed (WR3). These patients are still asymptomatic. At stage WR4, however, the seropositive patient is defined as no longer being asymptomatic but may be defined as having AIDS. For a further description of the Walter Reed Classification System and the clinical aspects of AIDS, see Redfield et al., Sci. Amer., 259:70 (1988).
While the Walter Reed Classification System provides a means for monitoring and staging the progress of an individual's disease, the system is based, at least initially, on the ability to quantify the number of CD4 cells present in a sample and/or detect the presence of anti HIV antibodies or virus in a sample. Unfortunately, currently available techniques for the detection of antibodies or virus have certain limitations. It is known, for example, to use recombinant or synthetic gp120 (an HIV viral envelope antigen) as a capture antigen in a serum based assay. This method, however, assumes that the progression of the disease in the individual is to such a state that not only are antibodies being made against HIV but that the antibodies made by the individual will react with synthetic gp120 and in sufficient quantity so as to be detectable. Indeed, early antibody responses may be masked by the presence of free virus in peripheral blood.
Similarly, using the reverse approach, antibodies against gp120 and other viral antigens (e.g., p24) may be made and used to detect the presence of virus or viral protein in a sample of blood from an individual. Although this is an antigen capture based method, its use assumes that the detecting antibodies will react with all forms of HIV which may be present in any particular infection and assumes that the viral particles are present in the serum sample; a limitation, however, is that virus particles are only transiently present in serum.
A further method for evaluating the serological response of an infected individual involves the use of the Western blotting technique wherein a serum sample derived from an individual is incubated with a piece of filter paper to which an electrophoretically separated preparation of HIV protein antigens have been fixed. If antibody is present in the serum sample then a precipitation product is generated and it may be assumed that antibodies are present to specific viral proteins. Again, this assay is based on the infected individuals serological response to the HIV virus.
Apart from these presently practiced techniques, other methods have been tried to identify HIV infection. Changes in the number of cellular immune effectors such as the number of CD4.sup.+ T cells or the ratio of CD4.sup.+ to CD8.sup.+ cells also have been used to identify and stage HIV infection. As noted above, the number of CD4.sup.+ T cells provides one basis for the Walter Reed Classification System. The ratio of CD4.sup.+ to CD8.sup.+ cells also may be indicative of the progression of the HIV infection. Finally, still other studies have reported that with HIV infection the number of HLA-DR+T cells or the number of CD8.sup.+ /CD38.sup.+ cells increases.
Because of the variable time course of appearance of certain of these markers and because of the potential unreliability of a number of these presently practiced techniques and often, a number of these techniques are used in concert in order to determine whether an individual has been exposed to HIV and has either made an antibody response or has the virus in the blood. This approach is both costly and time consuming.
In all cases, it is important to determine the transition from asymptomatic seropositive to AIDS. Knowing when this transition occurs will allow the physician to prescribe a more rigorous course of treatment. Accordingly, a rapid/early and reliable means for detecting the transition from a condition of asymptomatic seropositive to AIDS in the course of HIV infection is needed.